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Summary: Transforming growth factor (TGF)-β1, the most abundant isoform of TGF-β have been implicated in various stages of carcinogenesis such as epithelial to mesenchymal transition, enhanced expression of metalloproteases, down-regulation of cellular adhesion molecule, increased tumor motility and angiogenesis as well as local and systemic immunosuppression leading to a more aggressive and metastatic behavior. We assessed the association of TGF-β1 functional genetic polymorphisms at codon 10 (869 T>C) and 25 (915 G>C) of exon 1 in 140 patients with tobacco-related oral squamous cell carcinoma (OSCC) and 120 normal subjects by PCR–RFLP. The frequency of 869 CC genotype and C allele were significantly higher in patients as compared to controls (Pc , 0.024 and 0.0004, respectively) while no significant difference was observed in the frequency of 915 CC genotype and C allele. In logistic regression analysis CC genotype (OR, 3.87; 95% CI, 1.78–8.41) and C allele (OR, 2.20; 95% CI 1.51–3.20) appeared as susceptible while TT genotype and T allele as protective. In addition C869–C915 haplotype with OR of 2.48 at 95% CI, 1.51–4.06 significantly (P =0.0003) increased the risk of tobacco-related OSCC in Asian Indians. [Copyright &y& Elsevier]